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Herein, a rapid electrochemical screening of yeasts (Saccharomyces cerevisiae) in vitro mode depending on their optical density, cultivation time and growth medium used was conducted in 3 min by palladium nanoparticles (Pd-NPs)-modified electrodes. Pd-NPs-modified electrodes operated in cyclic voltammetry mode at low scan rates, i.e. 5-20 mV/s supported a low oxidative process in the yeast extracellular matrix. The electrochemical screening relied on an efficient electrooxidation of secondary metabolites, i.e. organohydrazines formed in the extracellular medium as a result of microbial activity of yeast cells. More importantly, during the study the impact of fundamental parameters, viz. type of the matrix and pH on electroanalytical response of Pd-NPs-based electrodes in real fermentation medium was investigated in detail. The efficiency of the proposed in vitro electrochemical screening of yeast extracellular matrix was not affected by pH of the samples or composition of the multicomponent medium, but more likely exclusively depended on the presence of organohydrazines. The potential of this electroanalytical approach towards profiling of the extracellular matrix of Saccharomyces cerevisiae was compared with results obtained by gas chromatography mass-spectrometry (GC-MS) and genetically encoded biosensor (ro-GFP2) assays.

Hypoglycemia is a common safety event when attempting to optimize glycemic control in diabetes (DM). While electronic medical records provide a natural ground for detecting and analyzing hypoglycemia, ICD codes used in the databases may be invalid, insensitive or non-specific in detecting new hypoglycemic events. We developed text preprocessing methods to improve automatic detection of hypoglycemia from analysis of clinical encounter text notes.We set out to improve hypoglycemia detection from clinical notes by introducing three preprocessing methods: stop word filtering, medication signaling, and ICD narrative enrichment. To test the proposed methods, we selected clinical notes from VA Maryland Healthcare System, based on various combinations of three criteria that are suggestive of hypoglycemia, including ICD-9 code of diabetes and hypoglycemia, laboratory glucose values70 md/dL, and text reference to a proximate hypoglycemia event. In addition, we constructed one dataset of 395 clinical notes from year 2009 and another of 460 notes from year 2014 to test the generality of the proposed methods. For each of the datasets, two physician judges manually reviewed individual clinical notes to determine whether hypoglycemia was present or absent. A third physician judge served as a final adjudicator for disagreements.Each of the proposed preprocessing methods contributed to the performance of hypoglycemia detection by significantly increasing the F1 score in the range of 5.3∼7.4% on one dataset (p .01). Among the methods, stop word filtering contributed most to the performance improvement (7.4%). Combining all the preprocessing methods led to greater performance gain (p .001) compared with using each method individually. Similar patterns were observed for the other dataset with the F1 score being increased in the range of 7.7%∼9.4% by individual methods (p .001). Nevertheless, combining the three methods did not yield additional performance gain.The proposed text preprocessing methods improved the performance of hypoglycemia detection from clinical text notes. Stop word filtering achieved the most performance improvement. ICD narrative enrichment boosted the recall of detection. Combining the three preprocessing methods led to additional performance gains.

RATIONALE & OBJECTIVE: Traditional risk estimates for atherosclerotic vascular disease (ASVD) and death may not perform optimally in the setting of CKD. We sought to determine whether the addition of measures of inflammation and kidney function to traditional estimation tools improves prediction of these events in a diverse cohort of patients with CKD. STUDY DESIGN: Observational cohort study SETTING & PARTICIPANTS: 2399 Chronic Renal Insufficiency Cohort (CRIC) study participants without history of cardiovascular disease at study entry. PREDICTORS: Baseline plasma levels of biomarkers of inflammation (interleukin (IL)-1β, IL-1RA (IL-1 receptor antagonist), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor β (TGFβ), high sensitivity C-Reactive protein (hs-CRP), fibrinogen, and serum albumin), measures of kidney function (estimated glomerular filtration rate (eGFR) and albuminuria), and the Pooled Cohort Equation Probability (PCEP) estimate. OUTCOMES: Composite of ASVD events (incident myocardial infarction (MI), peripheral arterial disease (PAD), and stroke) and death. ANALYTICAL APPROACH: Cox proportional hazard models adjusted for PCEP estimates, albuminuria, and eGFR. RESULTS: During a median follow-up of 7.3 years, 86, 61, 48, and 323 participants experienced MI, PAD, stroke, or death, respectively. 1-decile greater levels of IL-6 (adjusted Hazard Ratio [aHR], 1.12; 95% CI, 1.08-1.16; p

Introduction: A cornerstone of kidney disease management is participation in guideline-recommended health behaviors. However, the relationship of these health behaviors with outcomes, and the identification of barriers to health behavior engagement, have not been described among younger and older adults with chronic kidney disease. Methods: Data from a cohort study of 5499 individuals with chronic kidney disease was used to identify health behavior patterns with latent class analysis stratified by age

Background Adverse Event (AE) ontology can be used to support interoperability and computer-assisted reasoning of AEs. Despite significant progress in developing biomedical ontologies, they are facing the obstacle of adoption partly because those ontologies are too general to meet the requirements of a specific domain. Understanding and representing of AEs for a specific domain such as Chronic Kidney Disease (CKD) has both theoretical and clinical significance. CKD patients are at a high risk for an array of disease-intervention specific AEs, and these in turn can contribute to disease progression unlike other diseases. This study proposes Disease Specific Ontology of Adverse Events (DSOAE) to address specific requirements of CKD, and applies it to different usage scenarios with real data. Methods We introduce a method for developing DSOAE through the extension and adaption of general ontologies by incorporating domain-specific information and usage requirements. It starts with specifying the goal and scope of a target domain (i.e. selecting seed ontologies), followed by identifying main AE classes and relations, extracting and creating classes and relations, aligning and identifying upper-level classes and lower-level classes, and finally populating the ontology with instances. Any of these steps may be repeated to refine the ontology. Results DSOAE contains 22 CKD-specific AE classes, which are grouped into two general categories: patient-reported AEs and biochemical/laboratory-related AEs. In addition, disease history and comorbidity classes as introduced in this study help model patient-related risk factors for AEs. With the support of DSOAE, we build a knowledge base of CKD-specific AEs using data from different sources (e.g. patient cohort data and social media), and apply the knowledge base to data analysis and data integration. Conclusions DSOAE enables the interoperability of AEs across different sources and supports the development of a knowledge base of domain-specific AEs. DSOAE can also meet the needs of different usage scenarios. The approach to constructing DSOAE is generalizable and can be used to develop AE ontology in other domains.

Heterogeneous product user populations are common across many safety–critical domains. Catering to variable user needs is critical for designing safe and effective systems. Despite this, it is common for a 1-size-fits-all approach to be applied in design for these populations. Quantifying risk of use error throughout the design process can justify design decisions that maximize system performance and safety. Many regulatory agencies require consideration of user variability in design validation activities. However, there are practical challenges for integrating variable users into these activities. Adequately representing populations requires significant time and monetary commitments for subject recruitment. In addition, population access may be difficult in some cases. In this work, an alternative to traditional human factors design validation efforts is presented. Expert elicitation is proposed as a cost-effective means to quantify heterogenous user performance in the formative product design stages. The approach relies on the generation of generic physical and cognitive tasks that can be applied across use cases. The approach is demonstrated on the diabetes population, specially focusing on medical device use. The output of the demonstration are performance distributions for 27 task-user group pairs that can be integrated into design validation efforts to identify human error risks that require mitigation.

Patients with chronic kidney disease (CKD) are at risk for complications both inherent to the disease and as a consequence of its treatment. The dangers that CKD patients face change across the spectrum of the disease. Providers who are well-versed in these safety threats are best poised to safeguard patients as their CKD progresses.

RATIONALE & OBJECTIVE: Digital and mobile health (mHealth) technologies improve patient-provider communication and increase information accessibility. We assessed technology use, attitudes toward using mHealth technologies, and the proficiency in using mHealth technologies among individuals with chronic kidney disease (CKD). STUDY DESIGN: Cross-sectional survey with open text responses SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort Study participants who completed current use and interest in using mHealth technologies questionnaires, and the eHealth literacy Survey (eHEALS). EXPOSURES: Participant characteristics OUTCOMES: Technology use (internet/email/smartphone/mHealth applications [apps]), interest in future mHealth use, and proficiency in using digital and mHealth technologies, or eHealth literacy, determined by eHEALS score. ANALYTIC APPROACH: Poisson regression and a qualitative content analysis of open-ended responses RESULTS: Study participants (N=932) had a mean age of 68 years, eGFR 54 ml/min/1.73m(2), and 59% were male. Approximately 70% reported current use of internet/email/smartphones, and 35% used mHealth apps; only 27% had adequate eHealth literacy (eHEALS score ≥32). Participants

MALDI-TOF is a chemistry analytical tool that has recently been deployed in the identification of microorganisms isolated from nosocomial environments. Its use in diagnostics has been extremely advantageous in terms of cost effectiveness, sample preparation easiness, turn-around time and result analysis accessibility. In the dairy industry, where mastitis causes great financial losses, a rapid diagnostic method such as MALDI-TOF could assist in the control and prevention program of mastitis, in addition to the sanitation and safety level of the dairy farms and processing facility. However, the diagnostic strengths and limitations of this test method require further understanding. In the present study, we prospectively compared MALDI-TOF MS to conventional 16S rDNA sequencing method for the identification of pathogens recovered from milk associated with clinical and subclinical bovine mastitis cases. Initially, 810 bacterial isolates were collected from raw milk samples over a period of three months. However, only the isolates (481) having both 16S rDNA sequencing and MALDI-TOF identification were included in the final phase of the study. Among the 481 milk isolates, a total of 26 genera (12 g-postive and 14 g-negative), including 71 different species, were taxonomically charecterized by 16S rDNA at the species level. Comparatively, MALDI-TOF identified 17 genera (9 g-positive and 8 g-negative) and 33 differernt species. Overall, 445 (93%) were putatively identified to the genus level by MALDI-TOF MS and 355 (74%) were identified to the species level, but no reliable identification was obtained for 16 (3.3%), and 20 (4.2%) discordant results were identified. Future studies may help to overcome the limitations of the MALDI database and additional sample preparation steps might help to reduce the number of discordances in identification. In conclusion, our results show that MALDI-TOF MS is a fast and reliable technique which has the potential to replace conventional identification methods for common mastitis pathogens, routinely isolated from raw milk. Thus it's adoption will strengthen the capacity, quality, and possibly the scope of diagnostic services to support the dairy industry.

Chronic kidney disease (CKD) patients have several features conferring upon them a high risk of adverse safety events, which are defined as incidents with unintended harm related to processes of care or medications. These characteristics include impaired renal function, polypharmacy, and frequent health system encounters. The consequences of such events in CKD can include new or prolonged hospitalization, accelerated renal function loss, acute kidney injury, end-stage renal disease and death. Health information technology administered via telemedicine presents opportunities for CKD patients to remotely communicate safety-related findings to providers for the purpose of improving their care. However, many CKD patients have limitations which hinder their use of telemedicine and access to the broad capabilities of health information technology. In this review we summarize previous assessments of the pre-dialysis CKD populations’ proficiency in using telemedicine modalities and describe the use of interactive voice-response system (IVRS) to gauge the safety phenotype of the CKD patient. We discuss the potential for expanded IVRS use in CKD to address the safety threats inherent to this population.

Persistent deficits in social behavior, motor behavior, and behavioral flexibility are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked moderate prenatal alcohol exposure (PAE) in the rat to deficits in these behavioral domains, which depend upon the ventrolateral frontal cortex (Hamilton et al., 2014) [20]. Manipulations of the social environment cause modifications of dendritic morphology and experience-dependent immediate early gene expression in ventrolateral frontal cortex (Hamilton et al., 2010) [19], and may yield positive behavioral outcomes following PAE. In the present study we evaluated the effects of housing PAE rats with non-exposed control rats on adult behavior. Rats of both sexes were either paired with a partner from the same prenatal treatment condition (ethanol or saccharin) or from the opposite condition (mixed housing condition). At four months of age (∼3 months after the housing manipulation commenced), social behavior, tongue protrusion, and behavioral flexibility in the Morris water task were measured as in (Hamilton et al., 2014) [20]. The behavioral effects of moderate PAE were primarily limited to males and were not ameliorated by housing with a non-ethanol exposed partner. Unexpectedly, social behavior, motor behavior, and spatial flexibility were adversely affected in control rats housed with a PAE rat (i.e., in mixed housing), indicating that housing with a PAE rat has broad behavioral consequences beyond the social domain. These observations provide further evidence that moderate PAE negatively affects social behavior, and underscore the importance of considering potential negative effects of housing with PAE animals on the behavior of critical comparison groups.

Health professionals generally intend to provide effective, safe care and do no harm. Since the Institute of Medicine’s 1999 report To Err is Human brought attention to the overwhelming number of preventable medical errors in hospitals, it has become apparent that numerous threats to patient safety exist. The report estimates that between 44,000 and 98,000 patients die yearly from preventable medical errors. This staggering statistic does not capture patients otherwise harmed, or those who had “near miss” events. Understanding the vulnerabilities of specific patient populations can help providers better protect these patients. Patients with chronic kidney disease (CKD) are at an inherently increased risk for adverse safety events. Patients with CKD, whether presenting with reduced glomerular filtration rate (GFR) or with kidney damage but preserved function, are at risk of complications from nephrotoxic medications and inappropriate drug dosing. These patients have complications like anemia, hypervolemia, and electrolyte imbalances, along with comorbid conditions like diabetes, hypertension, and heart disease, which prompt frequent health care encounters, thereby increasing patients’ risk for adverse events. Moreover, adverse safety events in CKD have the potential to accelerate loss of kidney function and may increase the risk of end stage renal disease (ESRD) beyond what is expected from the disease’s natural history. Defining adverse safety events in CKD requires a nomenclature that incorporates various dimensions of safety as they relate to the disease. Box 1 distinguishes between adverse events and safety hazards. The former represent harmful clinical occurrences that are consequences of well-intentioned medical care (as opposed to the natural disease process). Safety hazards include ill-advised practices, omissions, or poorly monitored care that raise the risk of an untoward complication. Box 1 Safety nomenclature for CKD care Adverse Events Definition: harm to patients which results from medical care Subtypes ◦ Patient-reported safety incidents (falls, bleeding, hypoglycemia) ◦ Safety findings (hypoglycemia, hyperkalemia, orthostasis) ◦ Condition-dependent safety events (acute kidney injury after surgery, congestive heart failure after IV fluids) Safety Hazards Definition: clinical practices with the potential to lead to unintended patient harm Subtypes ◦ Errors of commission ▪ Definition: harm results from an action taken ▪ Examples: use of known nephrotoxins, improperly-dosed medications ◦ Errors of omission ▪ Definition: failure to provide care results in harm ▪ Example: use of an ACE inhibitor ◦ Use of therapies that require monitoring to mitigate harm ▪ Examples: diuretic, RAAS blocker, erythropoetic-stimulating agent, digoxin Near Miss Definition: event that did not cause patient harm, but only because of chance View it in a separate window Abbreviations: CKD, chronic kidney disease; IV, intravenous; ACE, angiotensin-converting enzyme; RAAS, renin-angiotensin-aldosterone system Compounding its enhanced risk for adverse safety events, CKD is often under-recognized by providers, particularly in elderly patients who may have a seemingly normal serum creatinine but significantly reduced GFR. Delayed recognition (or under-appreciation) of reduced GFR may postpone the initiation of therapies that slow CKD progression, as well as interfere with proper dosing of medications and avoidance of nephrotoxins. The National Kidney Disease Education Program (NKDEP) was launched in 2003 to raise awareness among primary care providers and high risk patients, and advocated for automatic reporting of estimated GFR (eGFR) along with serum creatinine in laboratory reports. Despite this effort, inappropriate medication dosing and nephrotoxic medication prescription among CKD patients persists. In this Core Curriculum, we review common complications of CKD management and medical interventions that pose significant threats to patient safety. Although dialysis patients and transplant recipients face unique health care dangers, we will focus on those issues specific to non-dialysis-dependent CKD.

Background In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD). Study Design Prospective cohort. Setting & Participants 3,006 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictors 4 lifestyle factors (regular physical activity, body mass index [BMI] of 20- 2 , nonsmoking, and "healthy diet"), individually and in combination. Outcomes CKD progression (50% decrease in estimated glomerular filtration rate or end-stage renal disease), atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease), and all-cause mortality. Measurements Multivariable-adjusted Cox proportional hazards. Results During a median follow-up of 4 years, we observed 726 CKD progression events, 355 atherosclerotic events, and 437 deaths. BMI≥25kg/m 2 and nonsmoking were associated with reduced risk of CKD progression (HRs of 0.75 [95% CI, 0.58-0.97] and 0.61 [95% CI, 0.45-0.82] for BMIs of 25 to 2 , respectively, versus 20 to 2 ; HR for nonsmoking of 0.68 [95% CI, 0.55-0.84] compared to the current smoker reference group) and reduced risk of atherosclerotic events (HRs of 0.67 [95% CI, 0.46-0.96] for BMI of 25- 2 and 0.55 [95% CI, 0.40-0.75] vs current smoker). Factors associated with reduced all-cause mortality were regular physical activity (HR, 0.64 [95% CI, 0.52-0.79] vs inactive), BMI≥30kg/m 2 (HR, 0.64 [95% CI, 0.43-0.96] vs 20- 2 ), and nonsmoking (HR, 0.45 [95% CI, 0.34-0.60] vs current smoker). BMI 2 was associated with increased all-cause mortality risk (HR, 2.11 [95% CI, 1.13-3.93] vs 20- 2 ). Adherence to all 4 lifestyle factors was associated with a 68% lower risk of all-cause mortality compared to adherence to no lifestyle factors (HR, 0.32; 95% CI, 0.11-0.89). Limitations Lifestyle factors were measured only once. Conclusions Regular physical activity, nonsmoking, and BMI≥25kg/m 2 were associated with lower risk of adverse outcomes in this cohort of individuals with CKD.

Persistent deficits in social behavior are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked deficits in social behavior following moderate prenatal alcohol exposure (PAE) in the rat to functional alterations in the ventrolateral frontal cortex [21]. In addition to social behaviors, the regions comprising the ventrolateral frontal cortex are critical for diverse processes ranging from orofacial motor movements to flexible alteration of behavior in the face of changing consequences. The broader behavioral implications of altered ventrolateral frontal cortex function following moderate PAE have, however, not been examined. In the present study we evaluated the consequences of moderate PAE on social behavior, tongue protrusion, and flexibility in a variant of the Morris water task that required modification of a well-established spatial response. PAE rats displayed deficits in tongue protrusion, reduced flexibility in the spatial domain, increased wrestling, and decreased investigation, indicating that several behaviors associated with ventrolateral frontal cortex function are impaired following moderate PAE. A linear discriminant analysis revealed that measures of wrestling and tongue protrusion provided the best discrimination of PAE rats from saccharin-exposed control rats. We also evaluated all behaviors in young adult (4-5 months) or older (10-11 months) rats to address the persistence of behavioral deficits in adulthood and possible interactions between early ethanol exposure and advancing age. Behavioral deficits in each domain persisted well into adulthood (10-11 months), however, there was no evidence that aging enhances the effects of moderate PAE within the age ranges that were studied.

Background Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized. Study Design Prospective cohort study. Setting & Participants The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race. Predictors Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors. Outcomes Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR 2 , (3) eGFR halving and 2 , (4) eGFR decrease of 20mL/min/1.73m 2 , (5) eGFR halving or decrease of 20mL/min/1.73m 2 , and (6) eGFR decrease of 25% and change in CKD stage. Results Mean entry eGFR was 44.9mL/min/1.73m 2 . Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively. Limitations Participants may not be representative of the entire CKD population. Conclusions Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.

Objectives To compare population-level baseline characteristics, individual-level utilization, and costs between antihypertensive medication users versus nonusers in adults with diabetes and concomitant hypertension. Methods This longitudinal retrospective observational research used Medical Expenditure Panel Survey household component pooled years 2006 to 2009 to analyze adults 18 years or older with nongestational diabetes and coexistent essential hypertension. Two groups were created: 1) antihypertensive medication users and 2) no antihypertensive pharmacotherapy. We examined average annualized health care costs and emergency department and hospital utilization. Accounting for Medical Expenditure Panel Survey's complex survey design, all analyses used longitudinal weights. Logistic regressions examined the likelihood of utilization and anytihypertensive medication use, and log-transformed multiple linear regression models assessed costs and antihypertensive medication use. Results Of the 3261 adults identified with diabetes, 66% (n = 2137) had concomitant hypertension representing 38.7 million individuals during 2006 to 2009. Significantly, the 16% (n = 338) no antihypertensive pharmacotherapy group showed greater mean nights hospitalized (3.6 vs. 1.7, P = 0.0120), greater all-cause hospitalization events per 1000 patient months (41 vs. 24, P = 0.0.007), and lower mean diabetes-related and hypertension-related ambulatory visits. After adjusting for confounders, non-antihypertensive medication users showed 1.64 odds of hospitalization, 29% lower total, and 27% lower average annualized medical expenses compared with antihypertensive medication users. Conclusions In adults with diabetes and coexistent hypertension, we observed significantly greater hospitalizations and lower costs for the non antihypertensive pharmacotherapy group versus those using antihypertensive medications. The short-term time horizon greater hospitalizations with lower expenses among non-antihypertensive medication users with diabetes and concomitant hypertension warrant further study.

To evaluate the diagnostic accuracy of 3 Tesla proton MRI for the assessment of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia.In a prospective study, 3 Tesla MRI was performed in 19 febrile neutropenic patients (5 women, 14 men; mean age 61 years ± 14.2; range 23-77 years). All patients underwent high-resolution CT less than 24h prior to MRI. The MRI protocol (Magnetom Tim Trio, Siemens) included a T2-weighted HASTE sequence (TE/TR: 49 ms/∞, slice thickness 6mm) and a high-resolution 3D VIBE sequence with an ultra-short TE1 ms (TE/TR 0.8/2.9 ms, slice thickness 2mm). The VIBE sequence was examined before and after intravenous injection of 0.1 mmol/kg gadoterate meglumine (Dotarem, Guerbet). The presence of pulmonary abnormalities, their location within the lung, and lesion type (nodules, consolidations, glass opacity areas) were analyzed by one reader and compared to the findings of HRCT, which was evaluated by a second independent radiologist who served as the reference standard. The findings were compared per lobe in each patient and rated as true positive (TP) findings if all three characteristics (presence, location, and lesion type) listed above were concordant to HRCT.Pulmonary abnormalities were characterized by 3 Tesla MRI with a sensitivity of 82.3% and a specificity of 78.6%, resulting in an overall accuracy of 88% (NPV/PPV 66.7%/89.5%). In 51 lobes (19 of 19 patients), pulmonary abnormalities visualized by MR were judged to be concordant in their location and in the lesion type identified by both readers. In 22 lobes (11 of 19 patients), no abnormalities were present on either MR or HRCT (true negative). In 6 lobes (5 of 19 patients), ground glass opacity areas were detected on MRI but were not visible on HRCT (false positives). In 11 lobes (7 of 19 patients), MRI failed to detect ground glass opacity areas identified by HRCT. However, since the abnormalities were disseminated in these patients, accurate treatment decisions were possible in every case based on MRI. In one case MRI showed a central area of cavitation, which was not visualized by HRCT.Infectious nodules and consolidations can be detected in neutropenic patients with acute myeloid leukemia with a sufficient diagnostic accuracy by 3 Tesla MRI. Detection of ground glass opacity areas is the main limitation of 3-Tesla MRI when compared to HRCT.

Lettuce and spinach are increasingly implicated in foodborne illness outbreaks due to contamination by Escherichia coli O157:H7. While this bacterium has been shown to colonize and survive on lettuce leaf surfaces, little is known about its interaction with the roots of growing lettuce plants. In these studies, a microarray analyses, mutant construction and confocal microscopy were used to gain an understanding of structure and function of bacterial genes involved in the colonization and growth of E. coli O157:H7 on lettuce roots. After three days of interaction with lettuce roots, 94 and 109 E. coli O157:H7 genes were significantly up- and down-regulated at least 1.5 fold, respectively. While genes involved in biofilm modulation (ycfR and ybiM) were significantly up-regulated, 40 of 109 (37%) of genes involved in protein synthesis were significantly repressed. E. coli O157:H7 was 2 logs less efficient in lettuce root colonization than was E. coli K12. We also unambiguously showed that a ΔycfR mutant of E. coli O157:H7 was unable to attach to or colonize lettuce roots. Taken together these results indicate that bacterial genes involved in attachment and biofilm formation are likely important for contamination of lettuce plants with Shiga toxin-producing E. coli strains.

To evaluate the effect of a temporal resolution improvement method (TRIM) for cardiac CT on diagnostic image quality for coronary artery assessment.The TRIM-algorithm employs an iterative approach to reconstruct images from less than 180° of projections and uses a histogram constraint to prevent the occurrence of limited-angle artifacts. This algorithm was applied in 11 obese patients (7 men, 67.2 ± 9.8 years) who had undergone second generation dual-source cardiac CT with 120 kV, 175-426 mAs, and 500 ms gantry rotation. All data were reconstructed with a temporal resolution of 250 ms using traditional filtered-back projection (FBP) and of 200 ms using the TRIM-algorithm. Contrast attenuation and contrast-to-noise-ratio (CNR) were measured in the ascending aorta. The presence and severity of coronary motion artifacts was rated on a 4-point Likert scale.All scans were considered of diagnostic quality. Mean BMI was 36 ± 3.6 kg/m(2). Average heart rate was 60 ± 9 bpm. Mean effective dose was 13.5 ± 4.6 mSv. When comparing FBP- and TRIM reconstructed series, the attenuation within the ascending aorta (392 ± 70.7 vs. 396.8 ± 70.1 HU, p0.05) and CNR (13.2 ± 3.2 vs. 11.7 ± 3.1, p0.05) were not significantly different. A total of 110 coronary segments were evaluated. All studies were deemed diagnostic; however, there was a significant (p0.05) difference in the severity score distribution of coronary motion artifacts between FBP (median=2.5) and TRIM (median=2.0) reconstructions.The algorithm evaluated here delivers diagnostic imaging quality of the coronary arteries despite 500 ms gantry rotation. Possible applications include improvement of cardiac imaging on slower gantry rotation systems or mitigation of the trade-off between temporal resolution and CNR in obese patients.

Chronic kidney disease is a high-risk condition for a variety of adverse safety events, yet little is known about differential rates of safety events across racial groups with decreased kidney function. We sought to examine the incidence of an array of disease-specific adverse safety events in black versus nonblack patients with decreased estimated glomerular filtration rate (eGFR).Retrospective observational study of a national US Veterans Affairs cohort.Veterans with eGFR60 mL/min/1.73 m(2) and one or more hospitalization during federal fiscal year 2005 (n = 70,154).Self-reported race/ethnicity dichotomized as black or nonblack.Hospital discharge coding for Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs), laboratory records for detection of hyperkalemia and hypoglycemia, and pharmacy records to determine dosing of 4 selected medications.Relationship between race and disease-specific patient safety events.Black veterans were more likely than nonblack veterans to experience one type of safety event (33% vs 32%, respectively) and multiple types of safety events (32% vs 23%, respectively; both P0.001). After adjustment, black veterans were 11% and 36% more likely to have at least one episode of hyperkalemia and hypoglycemia, respectively, than nonblack veterans, but were 14% less likely to experience a medication error (all P0.001). There was no association between the occurrence of AHRQ PSIs and race after adjustment.Use of administrative data has a risk of imprecision in coding; Veterans Affairs cohort may limit generalizability.Black veterans with decreased eGFR are more likely to experience a broad array of safety events than nonblacks with decreased eGFR, with a preponderance of metabolic disturbances rather than medication errors or AHRQ PSIs. The differential safety phenotype in blacks versus nonblacks may have implications for preventive strategies to improve patient safety in an integrated health care system.

Saccharomyces cerevisiae Esc2p is a member of a conserved family of proteins that contain small ubiquitin-like modifier (SUMO)-like domains. It has been implicated in transcriptional silencing and shown to interact with the silencing protein Sir2p in a two-hybrid analysis. However, little is known about how Esc2p regulates the structure of silent chromatin. We demonstrate here that ESC2 differentially regulates silent chromatin at telomeric, rDNA, and HM loci. Specifically, ESC2 is required for efficient telomeric silencing and Sir2p association with telomeric silent chromatin and for silencing and maintenance of silent chromatin structure at rDNA. On the other hand, ESC2 negatively regulates silencing at HML and HMR and destabilizes HML silent chromatin without affecting Sir2p association with chromatin. We present evidence that Esc2p is associated with both transcriptionally silent and active loci in the genome, and the abundance of Esc2p is not correlated with the chromatin state at a particular locus. Using affinity pull-down analyses, we show that Esc2p and Sir2p interact in vivo, and recombinant Esc2p and Sir2p interact directly. Moreover, we dissect Esc2p and identify a putative SUMO-binding motif that is necessary and sufficient for interacting with Sir2p and SUMO and is required for the function of Esc2p in transcriptional silencing.

A ionization technique in mass spectrometry called Direct Analysis in Real Time Mass Spectrometry (DART TOF-MS) coupled with a Direct Binding Assay was used to identify and characterize anti-viral components of an elderberry fruit (Sambucus nigra L.) extract without either derivatization or separation by standard chromatographic techniques. The elderberry extract inhibited Human Influenza A (H1N1) infection in vitro with an IC(50) value of 252+/-34 microg/mL. The Direct Binding Assay established that flavonoids from the elderberry extract bind to H1N1 virions and, when bound, block the ability of the viruses to infect host cells. Two compounds were identified, 5,7,3',4'-tetra-O-methylquercetin (1) and 5,7-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxycyclohexanecarboxylate (2), as H1N1-bound chemical species. Compound 1 and dihydromyricetin (3), the corresponding 3-hydroxyflavonone of 2, were synthesized and shown to inhibit H1N1 infection in vitro by binding to H1N1 virions, blocking host cell entry and/or recognition. Compound 1 gave an IC(50) of 0.13 microg/mL (0.36 microM) for H1N1 infection inhibition, while dihydromyricetin (3) achieved an IC(50) of 2.8 microg/mL (8.7 microM). The H1N1 inhibition activities of the elderberry flavonoids compare favorably to the known anti-influenza activities of Oseltamivir (Tamiflu; 0.32 microM) and Amantadine (27 microM).

Background Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the pathogenesis of kidney disease; however, their relation with level of kidney function has not been well characterized. Study Design Cross-sectional and prospective. Setting & Participants 548 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, MD. Predictor Serum carboxymethyl-lysine (CML), a dominant AGE; total soluble RAGE (sRAGE); and endogenous secretory RAGE (esRAGE). Outcomes & Measurements Glomerular filtration rate (GFR), prevalent and incident decreased GFR (GFR 2 ). Serum CML, sRAGE, and esRAGE. Results Of 548 women, 283 (51.6%) had decreased GFR at baseline. Serum CML level was associated with decreased GFR (OR [all expressed per 1 SD], 1.98; 95% CI, 1.41 to 2.76; P 1c level, and chronic diseases. Serum sRAGE and esRAGE levels (both in nanograms per milliliter) were associated with decreased GFR (OR, 1.42; 95% CI, 1.12 to 1.79; P = 0.003; OR, 1.42; 95% CI, 1.14 to 1.77; P = 0.001, respectively) in separate multivariate logistic regression models adjusting for potential confounders. Of 230 women without decreased GFR at baseline, 32 (13.9%) developed decreased GFR by the follow-up visit 12 months later. Serum CML (in micrograms per milliliter), sRAGE, and esRAGE levels at baseline were associated with the prevalence of decreased GFR 12 months later (OR, 1.80; 95% CI, 1.19 to 2.71; P = 0.005; OR, 1.32; 95% CI, 1.01 to 1.74; P = 0.05; and OR, 1.33; 95% CI, 1.01 to 1.77; P = 0.05, respectively) in separate multivariate logistic regression models adjusting for potential confounders. Limitations Small number of incident cases, limited follow-up, creatinine values not standardized. Conclusions AGE and circulating RAGE levels are independently associated with decreased GFR and seem to predict decreased GFR. AGEs are amenable to interventions because serum AGE levels can be decreased by change in dietary pattern and pharmacological treatment.

This paper investigates the influences of customer performance and environmental uncertainty on the customer's choice of relational exchange strategies over the duration of their relationship. Relational exchanges of short, intermediate, and long term duration are investigated with the results showing different performance outcomes and environmental factors impacting relational choice at different times in the relationship. The results help explain conflicts reported in prior relational exchange research and provide valuable insights for practitioners responsible for managing relational exchanges.

Background Little is known about how urea reduction ratio (URR) and hemoglobin (Hb) level relate as clinical performance measures (CPMs) in dialysis facilities. This study examined the relationship between these CPMs as a reflection of underlying processes. Study Design Cross-sectional observational. Setting & Participants 47,465 records from 18,003 patients dialyzed in 270 End-Stage Renal Disease Network 5 facilities during the final quarter of 2004. Predictor & Outcome Facility aggregate Hb level and URR, respectively; both expressed as (1) continuous variables and (2) dichotomous indicators based on established quality thresholds. Measurements Weighted regression analyses were used to determine the: (1) association between CPMs and (2) likelihood of missing the performance threshold for one if also missing the other benchmark. Results The association between facility URR and Hb level was minimal, with an adjusted mean increase (β) in URR of 0.91% ± 0.38% for each 1-g/dL increment in Hb level (P Limitations Inability to incorporate historic performance or ascertain facility process traits that influence CPMs. Conclusions There was minimal association between facility URR and Hb level. The limited concordance in facility performance for these CPMs points to distinct processes that determine quality for each.

The ability to noninvasively observe translational diffusion of proteins and protein complexes is important to many biophysical problems. We report high signal/noise (≥250) measurements of the translational diffusion in viscous solution of the fluorescent protein, DsRed. This is carried out using a new technique: molecular Fourier imaging correlation spectroscopy (M-FICS). M-FICS is an interferometric method that detects a collective Fourier component of the fluctuating density of a small population of fluorescent molecules, and provides information about the distribution of molecular diffusivities. A theoretical analysis is presented that expresses the detected signal fluctuations in terms of the relevant time-correlation functions for molecular translational diffusion. Furthermore, the role played by optical orientational degrees of freedom is established. We report Fickian self-diffusion of the DsRed tetramer at short timescales. The long-time deviation of our data from Fickian behavior is used to determine the variance of the distribution of the protein self-diffusion coefficient. We compare our results to the expected outcomes for 1), a bi-disperse distribution of protein species, and 2), dynamic disorder of the host solvent.

Modeling and simulation of the calcium signaling events that precede long-term depression of synaptic activity in cerebellar Purkinje cells are performed using the Virtual Cell biological modeling framework. It is found that the unusually high density and low sensitivity of inositol-1,4,5-trisphosphate receptors (IP3R) are critical to the ability of the cell to generate and localize a calcium spike in a single dendritic spine. The results also demonstrate the model’s capability to simulate the supralinear calcium spike observed experimentally during coincident activation of the parallel and climbing fibers. The sensitivity of the calcium spikes to certain biological and geometrical effects is investigated as well as the mechanisms that underlie the cell’s ability to generate the supralinear spike. The sensitivity of calcium release rates from the IP3R to calcium concentrations, as well as IP3 concentrations, allows the calcium spike to form. The diffusion barrier caused by the small radius of the spine neck is shown to be important, as a threshold radius is observed above which a spike cannot be formed. Additionally, the calcium buffer capacity and diffusion rates from the spine are found to be important parameters in shaping the calcium spike.

Cerebellar Purkinje neurons and neuroblastoma N1E-115 cells require 10-50 times more InsP3 to induce Ca2+ release than do a variety of non-neuronal cells (including astrocytes, hepatocytes, endothelial cells, or smooth muscle cells). Given the importance of InsP3-induced Ca2+ release for the development of synaptic plasticity in Purkinje neurons, a low InsP3 sensitivity may facilitate the integration of numerous synaptic inputs before initiating a change in synaptic strength. In the present study, attention is directed at the mechanism underlying this low InsP3 sensitivity of Ca2+ release. We show that permeabilization of neuroblastoma cells with saponin increased InsP3 sensitivity of Ca2+ release, indicating the presence of a diffusible, cytosolic inhibitor(s) of Ca2+ release. Consistent with this hypothesis, gel filtration of the neuroblastoma cytosol yielded three peaks that inhibited InsP3-induced Ca2+ release from permeabilized cells. The prominent inhibitory peak decreased the InsP3 sensitivity of Ca2+ release from permeabilized cells, did not bind 3H-InsP3, and was present in sufficient levels to account for the low InsP3 sensitivity of Ca2+ release in intact neuroblastoma cells. Purification of this prominent inhibitory fraction yielded a protein band that was identified by mass spectrometry as stress-induced phosphoprotein 1 (mSTI1). Furthermore, immunoprecipitation of mSTI1 decreased the inhibitory activity of N1E-115 cytosol, indicating that mSTI1 contributes to the inhibition of InsP3-induced Ca2+ release. Thus, the low InsP3 sensitivity of Ca2+ release in neuroblastoma cells can be explained by the presence of cytosolic inhibitors of Ca2+ release and include stress-induced phosphoprotein 1.

This study compares specific acceptance-based strategies and cognitive-control-based strategies for coping with experimentally induced pain. Forty participants were randomly assigned to an acceptance-based protocol (ACT), the goal of which was to disconnect pain-related thoughts and feelings from literal actions, or to a control-based protocol (CONT) that focused on changing or controlling pain-related thoughts and feelings. Participants took part in a nonsense-syllables-matching task that involved successive exposures to increasingly painful shocks. In both conditions, the task involved an overall value-oriented context that encouraged the participants to continue with the task despite the exposure to pain. At times throughout the task, participants were asked to choose to continue with the task and be shocked or stop the task and avoid being shocked. Each choice had specific costs and benefits. Participants performed the task twice, both before and after receiving the assigned experimental protocol. Two measures were obtained at pre- and post-intervention: tolerance of the shocks and self-reports of pain. ACT participants showed significantly higher tolerance to pain and lower believability of experienced pain compared to the CONT condition. Conceptual and clinical implications are discussed.

Neurite extension and branching are important neuronal plasticity mechanisms that can lead to the addition of synaptic contacts in developing neurons and changes in the number of synapses in mature neurons. Here we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates movement, extension, and branching of filopodia and fine dendrites as well as the number of synapses in hippocampal neurons. Only CaMKIIbeta, which peaks in expression early in development, but not CaMKIIalpha, has this morphogenic activity. A small insert in CaMKIIbeta, which is absent in CaMKIIalpha, confers regulated F-actin localization to the enzyme and enables selective upregulation of dendritic motility. These results show that the two main neuronal CaMKII isoforms have markedly different roles in neuronal plasticity, with CaMKIIalpha regulating synaptic strength and CaMKIIbeta controlling the dendritic morphology and number of synapses.

This study assesses whether the phylogenetic relationships between SODs from different organisms could assist in elucidating the functional relationships among these enzymes from evolutionarily distinct species. Phylogenetic trees and intron positions were compared to determine the relationships among these enzymes. Alignment of Cu/ZnSOD amino acid sequences indicates high homology among plant sequences, with some features that distinguish chloroplastic from cytosolic Cu/ZnSODs. Among eukaryotes, the plant SODs group together. Alignment of the Mn and FeSOD amino acid sequences indicates a higher degree of homology within the group of MnSODs (>70%) than within FeSODs (approximately 60%). Tree topologies are similar and reflect the taxonomic classification of the corresponding species. Intron number and position in the Cu/Zn Sod genes are highly conserved in plants. Genes encoding cytosolic SODs have seven introns and genes encoding chloroplastic SODs have eight introns, except the chloroplastic maize Sod1, which has seven. In Mn Sod genes the number and position of introns are highly conserved among plant species, but not among nonplant species. The link between the phylogenetic relationships and SOD functions remains unclear. Our findings suggest that the 5' region of these genes played a pivotal role in the evolution of function of these enzymes. Nevertheless, the system of SODs is highly structured and it is critical to understand the physiological differences between the SODs in response to different stresses in order to compare their functions and evolutionary history.

For future devices in metal oxide semiconductor technology there is a great interest in down scaling of device dimensions to improve device performance and to increase packing density. New device designs with nonuniform channel doping profiles are investigated to further enhance performance over conventional device designs and to suppress short channel effects. In this work we report sub-100 nm MOS devices with channel delta doping profiles grown using molecular beam epitaxy. Electrical characteristics and carrier transport in these devices are investigated and show significant improvements compared to conventional devices. Sharp channel profiles facilitate control of electric field and this “field engineering” improve the breakdown characteristics and provide better control of threshold voltage.

One major goal in power device research is the reduction of power losses while keeping high breakdown voltages. Commonly used power devices, e.g. DMOS™, use a combination of lateral channel and vertical drift zone. This involves power losses that can be reduced by a device concept with vertical channel and drift zone. We will discuss the classical DMOS™ structure in comparison with our vertical power device concept which was investigated with molecular beam epitaxy grown doping structures. The results show the influence of the channel design, i.e. homogeneous channel doping versus local channel doping, and its effect on the state-on resistance. Computer simulations help understand the advantages of the vertical concept and the improvement of the state-on resistance by local channel doping. For the channel design it is furthermore interesting to study the influence of the position of the local doping inside the channel on the device characteristics. The optimization of the channel design realized in a vertical device paves the way for size reduction of power devices and offers therefore first insights into the physical limits of the vertical concept.

The morphological features of polyoma virus disease (PVDz) in 571 concurrent urine and biopsy samples from 413 patients are described. In 54 patients PV was found in both biopsy and urine samples. Histologically, PV presented as: (a) mild, viral cytopathic/cytolytic changes, with absent or minimal inflammation involving isolated tubules; (b) moderate and severe, cytopathic/cytolytic changes associated with patchy or diffuse tubulo-interstitial inflammation and atrophy; (c) advanced, graft sclerosis with rare or absent viral cytopathic changes, indistinguishable from chronic allograft nephropathy. Histological progression from mild to moderate or severe disease was seen in 28 patients. The mean post-transplantation time at diagnosis was similar in patients with mild or moderate-severe renal involvement (1.05 and 1.3 years, respectively). All patients presented with similarly increased values of serum creatinine (mean 1.35 mg/dL). There was strong correlation between the number of PV infected cells in urine and the concurrent biopsies (p = 0.0001). In 13 patients PV was found only in urine; of these, two developed PVDz later. The positive predictive value of a positive urine was 90%, the negative predictive value of a negative urine was 99% and the accuracy of the test was 97%. We conclude that urine cytology is useful to evaluate renal transplant patients with PV reactivation because sloughed tubular cells are found in urine and positive urine samples are a consistent manifestation of PV renal involvement.

Caring for the urban renal patient can be a challenge to providers for many reasons. Although racial and socioeconomic factors have an impact on the health of this population, one must also consider the effect of the urban environment on the ill, especially those with renal disease. This article reviews the state of health among the poor and nonwhite minorities, who tend to inhabit the urban regions of this country, and then highlights the unique characteristics of those with renal disease. The impact of the Medicare end-stage renal disease (ESRD) program and center-specific quality of care on the outcome of the urban patient with ESRD is explored.

Erythropoietin (EPO) is recommended in individuals progressing toward end-stage renal disease (ESRD) to correct anemia and its complications, which are common in this disease. This study evaluated the impact of EPO administered before dialysis on mortality in incident ESRD patients. A total of 4,866 patients whose exposure to pre-ESRD EPO was determined from Health Care Financing Administration 2728 forms were analyzed. The median follow-up was 26.2 months, with 1,107 (22.7%) patients given EPO and 1,892 (38.9%) deaths. EPO use was more common in patients who had insurance before dialysis, remained employed, were started on renal replacement therapy outside the hospital, or initiated on peritoneal dialysis, which could be indicative of early intervention or quality care. The risk of death after starting dialysis was lower for patients treated with EPO before dialysis compared with patients who were not treated (adjusted relative risk 0.80, 95% confidence interval 0.70 to 0.91). There was no direct relationship between predialysis hematocrit and mortality; however, the most significant survival benefit with EPO use was in patients with the highest hematocrit values (adjusted relative risk 0.67, 95% confidence interval, 0.51 to 0.89). The most significant effect of pre-ESRD EPO use was observed during the first 19 months after starting dialysis (adjusted relative risk, 0.81; 95% confidence interval, 0.71 to 0.91), but this benefit diminished in patients with longer follow-up on renal replacement therapy. Use of EPO before dialysis confers a survival benefit to ESRD patients, especially in patients with an adequate hematocrit response before initiation of dialysis.

With the demographic shift in the U.S. to an older and heavier population, there has been a well-documented increase in the incidence of diabetes mellitus ([1][1]). Paralleling this rise in diabetes has been a growth in the number of Americans with chronic kidney disease (CKD). Estimates of the

Tunneling devices are an interesting alternative to conventional MOS-devices due to their high speed switching capabilities. Recently, it was shown that tunneling transistors based on vertical MOS-gated pin-diodes can be fabricated. The pin-diodes themselves were grown by means of UHV-MBE on highly n+-doped Si(100)-substrates with a 100 nm thick intrinsic channel region. The top contact was formed by the deposition of a highly-doped B δ-layer with a peak doping amount of approximately 1021 cm−3 for the necessary abrupt pn-junction and 300-nm p+-contact region. At a low supply voltage of −0.2 V, a current gain of three orders of magnitude with saturation behavior is achieved [1] . In the present contribution, we have shown the influence of the amount of B in the δ-layer and of the abruptness of the drain-channel-junction on the transistor behavior. For that, we have discussed the characteristics of MOS-gated pin-diodes on Si(111) with ultra-sharp B δ's with a peak doping amount between 1020 and 1021 cm−3 and a peak width [1] . In order to obtain these highly doped ultra-sharp B δ-layers, a phase-transition from an electrically inactive Si(111)- 3 × 3 -R30° B surface phase into an electrically active one was induced by rapid thermal annealing.

In this work we present a new approach for solving the tradeoff between breakdown capability and on state resistance for Power-MOS devices. Therefore we use a vertical transistor on an epitaxial layer. This concept allows the adjustment of the breakdown voltage due to the thickness of the epi-layer separately from the on-state resistance, which is defined by the vertical transistor. The transistor was fabricated by means of MBE, which allows very small channel length and doping control on atomistic scale. Devices with breakdown voltages between 12 V and 40 V were produced. It is also shown that the usage of local channel doping instead of homogenous doping in the switching transistor reduces the on state resistance of the device significantly.

Calcium waves produced by bradykinin-induced inositol-1,4, 5-trisphosphate (InsP(3))-mediated release from endoplasmic reticulum (ER) have been imaged in N1E-115 neuroblastoma cells. A model of this process was built using the "virtual cell," a general computational system for integrating experimental image, biochemical, and electrophysiological data. The model geometry was based on a cell for which the calcium wave had been experimentally recorded. The distributions of the relevant cellular components [InsP(3) receptor (InsP(3)R)], sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pumps, bradykinin receptors, and ER] were based on 3D confocal immunofluorescence images. Wherever possible, known biochemical and electrophysiological data were used to constrain the model. The simulation closely matched the spatial and temporal characteristics of the experimental calcium wave. Predictions on different patterns of calcium signals after InsP(3) uncaging or for different cell geometries were confirmed experimentally, thus helping to validate the model. Models in which the spatial distributions of key components are altered suggest that initiation of the wave in the center of the neurite derives from an interplay of soma-biased ER distribution and InsP(3) generation biased toward the neurite. Simulations demonstrate that mobile buffers (like the indicator fura-2) significantly delay initiation and lower the amplitude of the wave. Analysis of the role played by calcium diffusion indicated that the speed of the wave is only slightly dependent on the ability of calcium to diffuse to and activate neighboring InsP(3) receptor sites.

We present results obtained by different analysis methods as scanning tunneling microscopy (STM), atomic force microscopy (AFM), grazing incidence small angle X-ray scattering (GISAXS), and elastic recoil detection (ERD) on two similar semiconductor structures grown by molecular beam epitaxy (1) Si(111) substrate/Si buffer layer/B layer with σ B = (2.6 + 8) × 10 14 cm -2 /Ge cap layer and (2) Si(111) substrate/Si buffer layer/B layer with σ B = (2.6 ± δ) × 10 14 cm -2 /Si cap layer. It will be shown that the deposition of B with concentrations up to 2.6 × 10 14 cm -2 leads to a breakdown of the 7 × 7 reconstructed Si surface of the buffer layer and the formation of a Si( 11 1)-√3 × √3R30°B surface phase (BSP) located on T 4 -sites. Furthermore it is shown that this BSP acts as a lubricant' for additional deposited adatoms (Si and Ge) at deposition temperatures